Lecture 27 - Nucleic Acids, DNA, and Chromosomes

Nucleic Acids, DNA, and Chromosomes - Notes

I. Overview of Nucleic Acids

• Nucleic acids are linear macromolecules composed of chains of nucleotides, first isolated from cell nuclei, characterized by their acidic nature, and found in all living organisms.
• Composed of Carbon, Hydrogen, Oxygen, Nitrogen, and Phosphorus.
• Functions:
  1. Repository of genetic information (inheritance).
  2. Guide protein synthesis (correct amino acid assembly).

II. Structure of Nucleotides

• Components of Nucleotides:
  1. Nitrogenous base
  2. Five-membered sugar
  3. 1-3 phosphate groups
• Types of Nitrogenous Bases:
  • Purines: Adenine (A), Guanine (G)
  • Pyrimidines: Cytosine (C), Thymine (T), Uracil (U)

III. Pentose Sugars in Nucleotides

• Ribose: In RNA with a hydroxyl group (-OH) on the 2' carbon.
• Deoxyribose: In DNA with a hydrogen atom (-H) on the 2' carbon.

IV. Nucleotide Linkage

• Nucleotides are linked via 5' to 3' phosphodiester bonds.
• The bond forms between the phosphate group at the 5' carbon of one nucleotide and the hydroxyl group on the 3' carbon of another nucleotide.

V. Formation of Nucleic Acids

• Nucleosides: Sugar + Base, formed by glycosidic bonds.
• Nucleotides: Sugar + Base + Phosphate(s).

VI. Nomenclature of Nucleotides/Nucleosides

• Based on the base and sugar, nucleotides are classified with specific names and abbreviations.
  • Example:
    • Adenosine = Adenine + Ribose
    • Deoxyadenosine = Adenine + Deoxyribose
    • AMP (Adenosine Monophosphate), dAMP (Deoxyadenosine Monophosphate)

VII. Characteristics of DNA Structure

1. Nucleotides contain A, G, T, C, deoxyribose sugar, and phosphate.
2. DNA is typically double-stranded and antiparallel.
3. Hydrogen bonds between bases (A-T: 2 H-bonds; C-G: 3 H-bonds).
4. GC content affects stability and melting temperature.

VIII. DNA Denaturation and Renaturation

• Denaturation: Occurs through heating or chemical agents, separating strands.
• Renaturation: The re-annealing of DNA strands.

IX. DNA Structural Variants

• B-DNA: Most common and stable form.
• A-DNA: Short and wide, dehydrated state.
• Z-DNA: Left-handed helix, flexible, and can occur in certain viral infections.

X. Differences between DNA and RNA

• RNA is typically single-stranded, containing ribose and uracil, while DNA is double-stranded, contains deoxyribose, and has thymine.
• RNA can catalyze biochemical reactions (ribozymes) unlike DNA.

XI. RNA Characteristics

1. Various forms include mRNA, rRNA, tRNA, siRNA, and miRNA.
2. RNA is less stable than DNA due to the 2' hydroxyl group in ribose, making it susceptible to hydrolysis.

XII. Viral Genomes

• RNA viruses like HIV exist with higher mutation rates due to lack of proofreading by RNA polymerase.

XIII. Topoisomerases and DNA Packaging

• Types of Topoisomerases:
  • Type I: Cleaves one strand to manage supercoiling.
  • Type II: Cleaves both strands, requires ATP.
• Importance of Supercoiling:
  1. Compacts DNA for storage in the nucleus.
  2. Prepares DNA for replication and transcription.

XIV. Chromatin Structure

• Eukaryotic DNA is packaged into chromatin:
  • Euchromatin: Loosely packed, transcriptionally active.
  • Heterochromatin: Tightly packed, transcriptionally inactive.

XV. Nucleosome Assembly

• Nucleosomes consist of DNA wrapped around histones and further compacted via supercoiling during cell division, enabling management of gene expression and DNA protection.

Clinical Applications of Nucleic Acids

• Nucleotide/ Nucleoside Analogs: Used in cancer treatment (e.g., 5-Fluorouracil, Acyclovir).
• Topoisomerase Inhibitors: Anticancer drugs that interfere with DNA replication.

Summary of Key Points

• DNA and RNA serve critical functions in genetic information storage and transmission.
• Their respective structures are intricately designed to facilitate these biological processes, including enzymatic actions and interactions with molecular machinery for replication, transcription, and cellular function.